Combining the ventilatory response to exercise and peak oxygen consumption is no better than peak oxygen consumption alone in predicting mortality in chronic heart failure

BACKGROUND: A low peak oxygen uptake (pVO(2)) and steep VE/VCO(2) slope are independently associated with a worse prognosis in patients with chronic heart failure (CHF). We wished to confirm whether combining these variables as a ratio would lead to a more accurate predictor of prognosis than using either alone. METHODS: 388 CHF patients completed a treadmill-based cardiopulmonary exercise test (CPET) to volitional exhaustion using a modified Bruce protocol. RESULTS: 212 CHF patients completed the CPET with a peak RER >or= 1.0. Of these, 48 patients died and one was transplanted during follow-up. In surviving patients, the median follow-up period was 42 months (IQR 34-49 months). The ratio VE/VCO(2) slope/pVO(2) was calculated for each individual and its ability to predict outcome compared with other variables. The Cox multivariable survival analysis showed that pVO(2) was the strongest independent predictor of mortality in CHF patients. CONCLUSION: Our study shows that the composite variable VE/VCO(2) slope/pVO(2) is a less effective prognosticator than pVO(2) alone in patients with CHF.     

心肺运动试验摄氧量恢复延迟对经皮冠状动脉介入治疗术后患者预后的影响

目的探讨心肺运动试验(CPET)摄氧量恢复延迟(VO₂RD)对经皮冠状动脉介入治疗(PCI)术后心电图运动试验阴性患者预后的影响。方法回顾性分析北京大学第三医院2018年1月至2019年9月在PCI术后半年内行CPET且心电图运动试验阴性患者1268例,收集患者的临床资料、冠状动脉造影及介入操作资料、实验室检查、超声心动图及CPET检查结果。所有患者通过门诊或电话随访,记录患者不良心血管事件,包括死亡、心肌梗死、卒中、短暂性脑缺血发作、非计划再次PCI、周围血管介入治疗、不稳定型心绞痛和急性心力衰竭事件引起的住院。采用多因素Cox回归分析探讨CPET VO₂RD是否影响PCI术后心电图运动试验阴性患者的预后。结果1268例入选患者中完成随访1218例,失访50例,随访14(10,20)个月,共发生不良心血管事件105例(8.6%)。不良事件组年龄[(62.4±9.9)岁比(60.3±10.2)岁,P=0.020]、不完全血运重建比例(42.9%比31.6%,P=0.022)以及合并高脂血症比例(79.0%比68.0%,P=0.020)均显著高于无不良事件组;糖化血红蛋白值[(7.3±1.1)%比(6.6±1.2)%,P=0.001]、空腹血糖[(7.1±2.6)mmol/L比(6.5±1.9)mmol/L,P=0.010]及N末端B型脑钠肽前体[107.5(50.1,399.8)pg/ml比88.2(39.2,225.0)pg/ml,P=0.017]显著高于无不良事件组;峰值心率[(121±18)次/分比(126±20)次/分,P=0.012]、无氧阈心率[(99±12)次/分比(102±14)次/分,P=0.029]和峰值摄氧量[(17.3±4.7)ml/(min·kg)比(18.7±2.1)ml/(min·kg),P=0.003]显著低于无不良事件组,二氧化碳通气当量斜率[(33.3±9.2)比(28.1±5.1),P=0.001]和VO₂RD[(21.4±4.5)s比(18.5±5.4)s,P=0.001]显著高于无不良事件组。多因素Cox回归分析显示VO₂RD>20 s(HR 1.594,95%CI 1.026~2.476,P=0.038)是PCI术后心电图运动试验阴性患者发生不良心血管事件的独立危险因素。结论PCI术后心电图运动试验阴性的患者仍有一定的不良心血管事件发生风险,CPET恢复期指标VO₂RD>20 s是此类患者发生不良心血管事件的独立预测因素。     

轻中度哮喘患者提高运动耐量可行性研究

目的 比较同等日常运动水平的轻、中度哮喘患者与健康志愿者的运动心肺功能;探讨静息深吸气量与大运动功率的关系。方法 轻、中度哮喘患者１９例和健康志愿者１９例接受了运动心肺功能试验。试验采用负荷递增运动方案,运动前测一秒钟用力呼气容积（ＦＥＶ１）、深吸气量（ＩＣ）,运动后监测ＦＥＶ１。运动中监测心率、氧耗量（ＶＯ２）、每分钟通气量（ＶＥ）、氧脉搏（Ｏ２－ｐｕｌｓｅ）、呼吸频率等。结果 哮喘患者运动后Ｆ     

Endothelial progenitor cells mobilization after maximal exercise according to heart failure severity

BACKGROUNDVascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure (CHF). Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular endothelium. They also have low levels of endothelial progenitor cells (EPCs). EPCs are bone marrow derived cells involved in endothelium regeneration, homeostasis, and neovascularization. Exercise has been shown to improve vasodilation and stimulate the mobilization of EPCs in healthy people and patients with cardiovascular comorbidities. However, the effects of exercise on EPCs in different stages of CHF remain under investigation.AIMTo evaluate the effect of a symptom-limited maximal cardiopulmonary exercise testing (CPET) on EPCs in CHF patients of different severity.METHODSForty-nine consecutive patients (41 males) with stable CHF [mean age (years): 56 ± 10, ejection fraction (EF, %): 32 ± 8, peak oxygen uptake (VO₂, mL/kg/min): 18.1 ± 4.4] underwent a CPET on a cycle ergometer. Venous blood was sampled before and after CPET. Five circulating endothelial populations were quantified by flow cytometry: Three subgroups of EPCs [CD34⁺/CD45^-/CD133⁺, CD34⁺/CD45^-/CD133⁺/VEGFR₂ and CD34⁺/CD133⁺/vascular endothelial growth factor receptor 2 (VEGFR₂)] and two subgroups of circulating endothelial cells (CD34⁺/CD45^-/CD133^- and CD34⁺/CD45^-/CD133^-/VEGFR₂). Patients were divided in two groups of severity according to the median value of peak VO₂ (18.0 mL/kg/min), predicted peak VO₂ (65.5%), ventilation/carbon dioxide output slope (32.5) and EF (reduced and mid-ranged EF). EPCs values are expressed as median (25th-75th percentiles) in cells/10⁶ enucleated cells.RESULTSPatients with lower peak VO₂ increased the mobilization of CD34⁺/CD45^-/CD133⁺ [pre CPET: 60 (25-76) vs post CPET: 90 (70-103) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD45^-/CD133⁺/VEGFR₂ [pre CPET: 1 (1-4) vs post CPET: 5 (3-8) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD45^-/CD133^- [pre CPET: 186 (141-361) vs post CPET: 488 (247-658) cells/10⁶ enucleated cells, P < 0.001] and CD34⁺/CD45^-/CD133^-/VEGFR₂ [pre CPET: 2 (1-2) vs post CPET: 3 (2-5) cells/10⁶ enucleated cells, P < 0.001], while patients with higher VO₂ increased the mobilization of CD34⁺/CD45^-/CD133⁺ [pre CPET: 42 (19-73) vs post CPET: 90 (39-118) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD45^-/CD133⁺/VEGFR₂ [pre CPET: 2 (1-3) vs post CPET: 6 (3-9) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD133⁺/VEGFR₂ [pre CPET: 10 (7-18) vs post CPET: 14 (10-19) cells/10⁶ enucleated cells, P < 0.01], CD34⁺/CD45^-/CD133^- [pre CPET: 218 (158-247) vs post CPET: 311 (254-569) cells/10⁶ enucleated cells, P < 0.001] and CD34⁺/CD45^-/CD133^-/VEGFR₂ [pre CPET: 1 (1-2) vs post CPET: 4 (2-6) cells/10⁶ enucleated cells, P < 0.001]. A similar increase in the mobilization of at least four out of five cellular populations was observed after maximal exercise within each severity group regarding predicted peak, ventilation/carbon dioxide output slope and EF as well (P < 0.05). However, there were no statistically significant differences in the mobilization of endothelial cellular populations between severity groups in each comparison (P > 0.05).CONCLUSIONOur study has shown an increased EPCs and circulating endothelial cells mobilization after maximal exercise in CHF patients, but this increase was not associated with syndrome severity. Further investigation, however, is needed.     

Biomechanical efficiency is decreased in heart failure during low-level steady state and maximal ramp exercise

BACKGROUND: Previous studies of biomechanical efficiency (external work/energy input--Watt/O(2) consumed) in heart failure (HF) using cardiopulmonary exercise testing (CPET) and magnetic resonance spectroscopy (MRS) have had discordant results with increased efficiency by CPET and decreased efficiency by MRS. AIMS: Compare biomechanical efficiency of HF subjects and normal controls during steady state (SS=35 W for 6 min) and ramp cycle ergometer exercise. The hypothesis was that HF subjects would have impaired biomechanical efficiency that correlated with HF symptoms. METHODS: Biomechanical efficiency used the actual Vo(2) during exercise and recovery. Gross (Vo(2) above zero), Net (Vo(2) above the resting Vo(2)) and Work (Vo(2) above the unloaded pedaling Vo(2)) efficiencies were calculated. RESULTS: HF subjects had an 18% higher Vo(2) during SS exercise (P=0.029). Biomechanical efficiency was reduced during SS exercise (gross -15%, P=0.019, net -15%, P=0.062, and work -35%, P=0.002). Gross Efficiency during SS exercise had the strongest correlation with HF symptoms (r=0.55). During ramp exercise gross (-26%), net (-10%) and work (-8%) biomechanical efficiency were all reduced (all P<0.05). The slope of the Vo(2)/Watt relationship during ramp exercise had the best correlation with HF symptoms (r=0.46). CONCLUSIONS: HF subjects have an increased O(2) cost/Watt during SS and ramp exercise that correlates with HF symptoms of fatigue and breathlessness. Methods to improve biomechanical efficiency in HF subjects by exercise training or medications may improve the symptoms and the impaired exercise capacity associated with HF.     

Influence of body fat distribution on oxygen uptake and pulmonary performance in morbidly obese females during exercise

OBJECTIVE: The aim of this study was to determine the effects of fat distribution on aerobic and ventilatory response to exercise testing in morbidly obese (MO) females. METHODOLOGY: The study population consisted of 164 MO females, 55% (n = 90) with upper body or abdominal adiposity (UBD), as defined by waist-hip circumference ratio (WHR) > or = 0.80, and 45% (n = 74) with lower body fat distribution (LBD) (WHR < 0.80). An incremental exercise testing on cycle ergometer was performed to determine the effect of exercise on oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE), tidal volume (VT), respiratory rate (fb) and heart rate (HR). RESULTS: Upper body adiposity individuals had significantly higher VO2 and VCO2 than LBD subjects (P < 0.05) from 0 watt (W) of pedalling up to their anaerobic threshold (AT) and maximal exercise. VE was significantly higher in UBD subjects compared with LBD subjects, from 20 W during exercise up to AT and peak work levels (P < 0.05). Upper body adiposity group also had a significantly higher fb than the LBD group at rest, after each workload and at AT and peak exercise work rates (P < 0.05). VT was lower in UBD subjects at free pedalling and up to AT and peak workload with significant difference at 60 and 80 W (P < 0.05). The anaerobic threshold, expressed as work rate, was significantly lower in the UBD subjects (P < 0.05) and peak workload achieved did not differ significantly between the two groups. CONCLUSIONS: Upper body adiposity subjects had higher oxygen requirement, more rapid and shallow breathing, higher ventilatory demand, but lower anaerobic threshold than the LBD individuals during progressive exercise. It suggests that the cardiopulmonary endurance to exercise in MO patients with upper body fat distribution is lower than in those with lower body fat distribution.     

Insulin resistance and maximal oxygen uptake

BACKGROUND: Type 2 diabetes, coronary atherosclerosis, and physical fitness all correlate with insulin resistance, but the relative importance of each component is unknown. HYPOTHESIS: This study was undertaken to determine the relationship between insulin resistance, maximal oxygen uptake, and the presence of either diabetes or ischemic heart disease. METHODS: The study population comprised 33 patients with and without diabetes and ischemic heart disease. Insulin resistance was measured by a hyperinsulinemic euglycemic clamp; maximal oxygen uptake was measured during a bicycle exercise test. RESULTS: There was a strong correlation between maximal oxygen uptake and insulin-stimulated glucose uptake (r = 0.7, p = 0.001), and maximal oxygen uptake was the only factor of importance for determining insulin sensitivity in a model, which also included the presence of diabetes and ischemic heart disease. CONCLUSION: Maximal oxygen uptake may be a more important determinant for insulin sensitivity than ischemic heart disease and type 2 diabetes.     

先天性心脏病患者运动心肺功能表现

目的探讨先天性心脏病患者运动负荷测验特点。方法15例患者，男4例，女11例。其中房缺9例，室缺6例。并与年龄相近健康男性4例、女性11例作对照。进行踏车递增负荷运动测验。结果先天性心脏病组VO2max，VO2max占预计值％（＜正常84％）低于对照组；VO2AT，VO2AT／VO2maxpred低于对照组但在正常范围内；此外VO2／HRmax＜VO2／HRmaxpred。有3例心导管证实为肺动脉高压者，运动后PaO2及SaO2减低；P（A－a）O2加宽；P（a－et）CO2正值；VE／VCO2AT异常增高超过45，但BRmax正常。结论先天性心脏病患者运动负荷表现为最大有氧代谢能力减低。VE／VCO2AT异常增高为肺动脉高压、V／Q比率失调、肺循环障碍提供线索。运动后低血氧考虑有右至左分流。     

Influence of cardiac functional capacity on gender differences in maximal oxygen uptake in children

OBJECTIVE: To examine the role of gender differences in cardiac functional capacity in explaining higher mean values for maximal oxygen uptake (VO(2)max) in boys than in girls. DESIGN: Comparative group exercise testing. SETTING: Pediatric exercise testing laboratory. SUBJECTS: Twenty-five prepubertal boys (mean [+/- SD] age, 12 +/- 0.4 years) and 24 premenarcheal girls (mean age, 11.7 +/- 0.5 years). INTERVENTIONS: Maximal incremental upright cycle exercise. MEASUREMENTS AND RESULTS: Mean values for VO(2)max were the following: boys, 47.2 +/- 6.1 mL/kg/min; and girls, 40.4 +/- 5.8 mL/kg/min (16.8% difference; p < 0.05). The average maximal stroke index with Doppler echocardiography was 62 +/- 9 mL/m(2) for boys and 55 +/- 9 mL/m(2) for girls (12.7% difference; p < 0.05). No significant gender differences were seen in maximal heart rate or arterial venous oxygen difference. When VO(2)max and maximal stroke volume (SV) were expressed relative to lean body mass, gender differences declined but persisted, falling to 6.2% and 5.2%, respectively. CONCLUSIONS: These findings indicate that differences in SV as well as in body composition contribute to gender-related variations in VO(2)max during childhood. Whether this reflects small gender differences in relative heart size or dynamic factors influencing ventricular preload and contractility during exercise is unknown.     

Prediction of peak oxygen pulse (O2Ppeak) without exercise testing in older adults

Peak oxygen pulse has been considered a surrogate of cardiovascular function and an independent predictor of all cause mortality. However, O₂P_peak depends on maximal volitional effort which may limit its utility in older subjects. The aim of this study was to develop a model to estimate O₂P_peak without exercise in an elderly sample. This cross-sectional study enrolled 67 community-dwelling older adults (69.4 ± 7.1 years; 41 men) for the non-exercise model development and 30 community-dwelling older adults (67.7 ± 6.4 years; n = 30; 17 men) for cross-validation. The non-exercise model was derived through hierarchical regression model and cross-validated by means of PRESS statistics and comparison against an independent sample. Classification accuracy of the model for tertiles of estimated and actual O₂P_peak was tested by gamma (γ) nonparametric correlation. The following prediction equation was generated: −3.416 + 0.137 × weight (kg) + 1.226 × Veterans Specific Activity Questionnaire (VSAQ) (metabolic equivalents, METs) + 1.987 × gender (0 = women, 1 = men) − 2.045 × β-Blockers use (0 = no, 1 = yes) − 0.044 × resting heart rate (HR) (R² = 0.83; standard error of estimate (SEE) = 1.68 mL beat⁻¹). Correlation in cross-validation group was 0.80 (P < 0.001). A high probability was observed for the model to rank the values in the same tertile in validation and cross-validation groups (γ = 0.98; γ = 0.92, respectively, P < 0.05). In conclusion, O₂P_peak can be estimated with reasonable precision without exercise testing, providing an alternative for elder subjects not capable to perform maximal effort.     

Early oxygen uptake recovery following exercise testing in children with chronic chest diseases

The value of exercise testing as an objective measure of disease severity in patients with chronic chest diseases (CCD) is becoming increasingly recognized. The aim of this study was to investigate changes in oxygen uptake during early recovery following maximal cardiopulmonary exercise testing (CPXT) in relation to functional capacity and markers of disease severity. Twenty‐seven children with CCD (age 12.7 ± 3.1 years; 17 female) [19 children with Cystic fibrosis (CF) (age 13.4 ± 3.1 years; 10 female) and 8 with other stable non‐CF chest diseases (NON‐CF) (age 11.1 ± 2.2 years; 7 female)] and 27 healthy controls (age 13.2 ± 3.3 years; 17 female) underwent CPXT on a cycle ergometer. On‐line respiratory gas analysis measured before and during CPXT to peak _peak, and during the first 10 min of recovery. Early recovery was quantified by the time (sec) to reach 50% of the _peak value. Early recovery was correlated against spirometry [forced expiratory volume in 1 sec (FEV₁) and forced expiratory flow between 25% and 75% of the forced vital capacity (FEF_25–75)] and aerobic fitness _peak as a measure of functional capacity. Disease severity was graded in the CF patients by the Shwachman score (SS). Compared to controls, children with CCD demonstrated a significantly reduced _peak (P = 0.011), FEV₁ (P < 0.001), FEF_25–75 (P < 0.001), and a significantly prolonged early recovery (P = 0.024). In the CF patients the SS was significantly correlated with early recovery (r = ?0.63, P = 0.004), FEV₁ (r = 0.72, P = 0.001), and FEF_25–75 (r = 0.57, P = 0.011). In the children with CCD, FEV₁, FEF_25–75, and BMI were not significantly correlated with _peak or early recovery. Lung function does not necessarily reflect aerobic fitness and the ability to recover from exercise in these patients. A significant relationship was found between _peak and early recovery (r = ?0.39, P = 0.044) in the children with CCD, showing that a greater aerobic fitness corresponded with a faster recovery. Pediatr Pulmonol. 2009; 44:480–488. © 2009 Wiley‐Liss, Inc.     

Usefulness of cardiopulmonary exercise testing to predict the development of arterial hypertension in adult patients with repaired isolated coarctation of the aorta

Background

Patients who underwent surgery for aortic coarctation (COA) have an increased risk of arterial hypertension. We aimed at evaluating (1) differences between hypertensive and non-hypertensive patients and (2) the value of cardiopulmonary exercise testing (CPET) to predict the development or progression of hypertension.

Methods

Between 1999 and 2010, CPET was performed in 223 COA-patients of whom 122 had resting blood pressures of < 140/90 mm Hg without medication, and 101 were considered hypertensive. Comparative statistics were performed. Cox regression analysis was used to assess the relation between demographic, clinical and exercise variables and the development/progression of hypertension.

Results

At baseline, hypertensive patients were older (p = 0.007), were more often male (p = 0.004) and had repair at later age (p = 0.008) when compared to normotensive patients. After 3.6 ± 1.2 years, 29/120 (25%) normotensive patients developed hypertension. In normotensives, VE/VCO₂-slope (p = 0.0016) and peak systolic blood pressure (SBP; p = 0.049) were significantly related to the development of hypertension during follow-up. Cut-off points related to higher risk for hypertension, based on best sensitivity and specificity, were defined as VE/VCO₂-slope ≥ 27 and peak SBP ≥ 220 mm Hg. In the hypertensive group, antihypertensive medication was started/extended in 48/101 (48%) patients. Only age was associated with the need to start/extend antihypertensive therapy in this group (p = 0.042).

Conclusions

Higher VE/VCO₂-slope and higher peak SBP are risk factors for the development of hypertension in adults with COA. Cardiopulmonary exercise testing may guide clinical decision making regarding close blood pressure control and preventive lifestyle recommendations.     

Impact of pulmonary regurgitation and right ventricular dysfunction on oxygen uptake recovery kinetics in repaired tetralogy of Fallot

BACKGROUND: Patients with repaired tetralogy of Fallot (ToF) featuring severe pulmonary regurgitation (PR) and/or right ventricular (RV) dysfunction have reduced exercise tolerance. AIMS: To assess the impact of PR and of RV function on the ability to recover from exercise in ToF patients. METHODS: 61 consecutive patients aged 23.1+/-12.1 years underwent maximal cardiopulmonary exercise test (CPX), transthoracic echocardiography and magnetic resonance imaging. This data was compared to those of 153 matched healthy subjects. RESULTS: 19 patients (31%) had severe PR. RV dysfunction was noted in 19 patients (31%). Nine patients (15%) had both severe PR and RV dysfunction. Patients had lower peak oxygen uptake (VO2), VO2 slope, carbon dioxide production (VCO2) slope and O2 pulse slope (p < 0.0001), especially those with severe PR and RV dysfunction (p < 0.0001). Heart rate slope was similar between groups. No patient with severe PR and RV dysfunction had a predicted peak VO2 > 40%. CPX had a high sensitivity and specificity to identify patients with severe PR and RV dysfunction. CONCLUSIONS: In ToF patients, severe PR and RV dysfunction lead to delayed recovery from exercise. CPX can identify patients with severe PR and RV dysfunction and may be useful to guide the pulmonary valve replacement decision-making process.     

Self-estimated physical functioning poorly predicts actual exercise capacity in adolescents and adults with congenital heart disease

Aims: The aim of this study is to compare self-reported health-relatedquality-of-life (HRQoL) with the objective of exercise performancein patients with congenital heart disease (CHD) according todiagnosis. Methods and results: 564 patients (255 females, 14–73 years) with various CHD(62 shunt, 66 left heart obstruction, 33 PS/PR, 47 Ebstein,96 Fallot, 98 TGA after atrial switch, 38 other TGA, 31 Fontan,32 palliated/native cyanotic, 61 others) and a group of 53 healthycontrols (18 females, 14–57 years) completed a QoL questionnaire(SF-36) and performed a symptom-limited cardiopulmonary exercisetest. Despite several limitations at exercise (P = 1.30 x 10^–33),patients only reported reductions in HRQoL concerning physicalfunctioning (P = 4.41 x 10^–15) and general health (P =6.17 x 10^–5) and not psychosocial aspects. This couldbe confirmed in all diagnostic subgroups. Correlation to peakoxygen uptake was found in physical functioning (r = 0.435,P = 1.72 x 10^–27) and general health (r = 0.275, P = 3.79x 10^–11). However, there was severe overestimation ofphysical functioning in most patients when compared with actualexercise test results. Conclusion: Patients with CHD rate their HRQoL impaired only in physicalfunctioning and general health and not in any psychosocial aspect.Self-estimated physical functioning poorly predicts actual exercisecapacity.     

Prediction of maximal oxygen uptake and power during cycle ergometry in subjects older than 55 years of age

One hundred twenty-eight healthy volunteers (81 women, 47 men) older than 55 yr of age were studied with an incremental progressive cycle ergometer test to a symptom-limited, maximal tolerable work load. Mean (+/- SD) age was 66 +/- 6 yr in women and 66 +/- 5 years in men. Subjects with a history of ischemic heart disease, diabetes, pulmonary disease, or neuromuscular disease were excluded. Smokers were included, but all subjects had normal FEV1 and FVC. The objective of the study was to compare measured values of VO2max and Wmax in this older population with previously published predicted values based on subjects of all ages. We found that Wmax observed exceeded Wmax predicted by 9.5 +/- 22% (mean +/- SD) and that VO2max observed exceeded VO2max predicted by 17.5 +/- 22%. Because of this systematic underestimate of VO2max and Wmax by the previous prediction equations, we constructed new prediction equations for use in subjects older than 55 yr of age using height, weight, age, and sex as variables. We conclude that these new prediction equations more accurately predict Wmax and VO2max in subjects older than 55 yr of age because they are based solely on subjects in this age group.     

The Relationship Between Leptin and Ventilatory Control in Heart Failure

BackgroundIncreased serum leptin concentration has been linked to increased ventilation in patients with mild heart failure (HF). However, in animal models the absence of leptin has also been associated with increased ventilation. This study evaluated the relationship of circulating leptin concentration with exercise ventilation in HF patients.Methods and ResultsFifty-eight consecutive ambulatory HF patients were stratified by quintiles of leptin concentration, with a lowest quintile of mean leptin concentration of 1.8 ± 8.9 ng/mL and a highest of 33.3 ± 30.3 ng/mL. Peak exercise ventilatory efficiency (VE/VCO₂) was significantly elevated in the lowest (46 ± 6 vs 34 ± 4; P < .01) as well as in the highest (38 ± 8 vs 34 ± 4; P < .05) leptin concentration quintiles compared with the reference middle quintile. Multiple regression analysis adjusted for confounders such as age, sex, and body mass index showed leptin concentration to be independently inversely correlated to VE/VCO₂ in the low-to-normal quintiles (β = ?0.64; P < .01), positively in the normal-to-high quintiles (β = 0.52; P = .02), and positively correlated to P_ETCO₂ in the low-to-normal quintiles (β = 0.59; P = .01) and inversely in the normal-to-high quintiles (β = ?0.53; P = .02).ConclusionsIn HF patients, both high and low leptin concentrations are associated with increased VE/VCO₂ and decreased P_ETCO₂ with a nonlinear U-shaped relationship, suggesting that either leptin deficiency or leptin resistance may modulate ventilatory control in HF patients.